The pharmacological interaction of compounds in ayahuasca: a systematic review

Ayahuasca is a South American psychoactive plant brew used as traditional medicine in spiritual and in cultural rituals. This is a review of the current understanding about the pharmacological mechanisms that may be interacting in ayahuasca. Searches were performed using PubMed, PsycINFO, and Web of Science databases and 16 papers were selected. As hypothesized, the primary narrative in existing research revolved around prevention of deamination of N,N-dimethyltryptamine (N,N-DMT, also referred to as DMT) by monoamine oxidase inhibitors (MAOIs) in ayahuasca. Two of the constituents, DMT and harmine, have been studied more than the secondary harmala alkaloids. At present, it is unclear whether the pharmacological interactions in ayahuasca act synergistically or additively to produce psychoactive drug effects. The included studies suggest that our current understanding of the preparation's synergistic mechanisms is limited and that more complex processes may be involved; there is not yet enough data to determine any potential synergistic interaction between the known compounds in ayahuasca. Our pharmacological understanding of its compounds must be increased to avoid the potential risks of ayahuasca use.

Antidepressive and anxiolytic effects of ayahuasca: a systematic literature review of animal and human studies

Objective: To conduct a systematic literature review of animal and human studies reporting anxiolytic or antidepressive effects of ayahuasca or some of its isolated alkaloids (dimethyltryptamine, harmine, tetrahydroharmine, and harmaline). Methods: Papers published until 3 April 2015 were retrieved from the PubMed, LILACS and SciELO databases following a comprehensive search strategy and using a predetermined set of criteria for article selection. Results: Five hundred and fourteen studies were identified, of which 21 met the established criteria. Studies in animals have shown anxiolytic and antidepressive effects of ayahuasca, harmine, and harmaline, and experimental studies in humans and mental health assessments of experienced ayahuasca consumers also suggest that ayahuasca is associated with reductions in anxiety and depressive symptoms. A pilot study reported rapid antidepressive effects of a single ayahuasca dose in six patients with recurrent depression. Conclusion: Considering the need for new drugs that produce fewer adverse effects and are more effective in reducing anxiety and depression symptomatology, the described effects of ayahuasca and its alkaloids should be further investigated.

Ayahuasca: uma revisão dos aspectos farmacológicos e toxicológicos / Ayahuasca: a review of pharmacological and toxicological aspects

A ayahuasca é uma bebida psicoativa originariamente utilizada em rituais de tribos indígenas da região amazônica. Esta bebida é preparada pela infusão de caules da Banisteriopsis caapi Morton, que contém Beta-carbolinas que são inibidoras da monoaminoxidase (MAO), e de folhas da Psychotria viridis Ruiz & Pavón, que contém o alucinógeno N,N-dimetiltriptamina (DMT). A enzima MAO degrada a DMT no fígado e intestino. No Brasil, a ayahuasca tem sido incorporada em rituais de grupos sincréticos religiosos e seu uso dentro do contexto religioso é amparado por lei federal. Atualmente, esses grupos têm se espalhado na Europa e Estados Unidos, chamando a atenção de pesquisadores internacionais quanto aos efeitos da ayahuasca. Estudos têm indicado que a ayahuasca poderia ter aplicações terapêuticas como no tratamento da farmacodependência e até sugerem seu uso seguro por adultos sadios. Entretanto, poucos estudos têm sido conduzidos para melhor avaliação de suas propriedades. O objetivo do artigo é mostrar uma revisão geral da história até as recentes descobertas envolvendo a farmacologia e a toxicologia da ayahuasca.

Ayahuasca (or caapi in Brazil) is a psychoactive plant beverage initially used by shamans in religious rituals practiced by indigenous peoples in the Amazon region. It is prepared by infusing the pounded stems of Banisteriopsis caapi Morton, a liana which contains beta-carbolines, alkaloids that are potent monoamine oxidase (MAO) inhibitors, together with the leaves of Psychotria viridis Ruiz & Pavón, which contains the psychedelic agent N,N-dimethyltryptamine (DMT). The enzyme MAO normally degrades DMT in the liver and gut. In Brazil, the use of ayahuasca within religious ceremonies is protected by law and it has been incorporated into rituals of syncretic religious groups. Some of these groups have established themselves in the United States and European countries, attracting international research interest in the effects of ayahuasca. Studies suggest that it may have therapeutic applications, such as in the treatment of drug addiction, and that it can be used safely by healthy adults. However, too few studies have been performed for a good assessment of its properties to be made. The aim of this article is to present a review of the history of ayahuasca, up to the recent discoveries concerning its pharmacology and toxicology.